Targeting a cell surface vitamin D receptor on tumor-associated macrophages in triple-negative breast cancer

被引：24

作者：

Staquicini, Fernanda, I ^{[1
,2
,26
]}

Hajitou, Amin ^{[3
]}

Driessen, Wouter H. P. ^{[4
,27
]}

Proneth, Bettina ^{[5
]}

Cardo-Vila, Marina ^{[6
,7
]}

Staquicini, Daniela, I ^{[1
,2
]}

Markosian, Christopher ^{[1
,2
]}

Hoh, Maria ^{[8
,28
]}

Cortez, Mauro ^{[9
]}

Hooda-Nehra, Anupama ^{[1
,10
]}

Jaloudi, Mohammed ^{[1
,10
]}

Silva, Israel T. ^{[11
]}

Buttura, Jaqueline ^{[11
]}

Nunes, Diana ^{[12
]}

Dias-Neto, Emmanuel ^{[11
,12
]}

Eckhardt, Bedrich ^{[13
]}

Ruiz-Ramirez, Javier ^{[14
]}

Dogra, Prashant ^{[14
]}

Wang, Zhihui ^{[14
]}

Cristini, Vittorio ^{[14
]}

Trepel, Martin ^{[15
,16
]}

Anderson, Robin ^{[13
]}

Sidman, Richard L. ^{[17
]}

Gelovani, Juri G. ^{[18
,19
,20
,29
]}

Cristofanilli, Massimo ^{[21
]}

Hortobagy, Gabriel ^{[22
]}

Bhujwalla, Zaver M. ^{[8
]}

Burley, Stephen ^{[23
,24
,25
]}

Arap, Wadih ^{[1
,10
]}

Pasqualini, Renata ^{[1
,2
]}

机构：

[1] Rutgers Canc Inst New Jersey, Newark, NJ 07103 USA

[2] Rutgers New Jersey Med Sch, Dept Radiat Oncol, Div Canc Biol, Newark, NJ 07103 USA

[3] Imperial Coll London, Dept Brain Sci, Phage Therapy Grp, London, England

[4] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA

[5] Helmholtz Zentrum Muenchen, Inst Metab & Cell Death, Neuherberg, Germany

[6] Univ Arizona, Canc Ctr, Dept Cellular & Mol Med, Tucson, AZ USA

[7] Univ Arizona, Canc Ctr, Dept Otolaryngol Head & Neck Surg, Tucson, AZ USA

[8] Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Div Canc Imaging Res, Baltimore, MD USA

[9] Univ Sao Paulo, Inst Biomed Sci, Dept Parasitol, Sao Paulo, SP, Brazil

[10] Rutgers New Jersey Med Sch, Dept Med, Div Hematol Oncol, Newark, NJ 07103 USA

[11] AC Camargo Canc Ctr, Lab Computat Biol, Sao Paulo, SP, Brazil

[12] AC Camargo Canc Ctr, Lab Med Genom, Sao Paulo, SP, Brazil

[13] Olivia Newton John Canc Res Inst, Translat Breast Canc Program, Melbourne, Vic, Australia

[14] Houston Methodist Res Inst, Math Med Program, Houston, TX USA

[15] Univ Med Ctr Hamburg Eppendorf, Dept Oncol & Hematol, Hamburg, Germany

[16] Univ Med Ctr Augsburg, Dept Oncol & Hematol, Augsburg, Germany

[17] Harvard Med Sch, Dept Neurol, Boston, MA 02115 USA

[18] Wayne State Univ, Coll Engn, Dept Biomed Engn, Detroit, MI USA

[19] Wayne State Univ, Sch Med, Dept Oncol, Detroit, MI USA

[20] Wayne State Univ, Sch Med, Dept Neurosurg, Detroit, MI USA

[21] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Feinberg Sch Med, Chicago, IL 60611 USA

[22] Univ Texas MD Anderson Canc Ctr, Dept Breast Med Oncol, Houston, TX 77030 USA

[23] Rutgers Canc Inst New Jersey, New Brunswick, NJ USA

[24] Univ Calif San Diego, San Diego Supercomp Ctr, Res Collab Struct Bioinformat Prot Data Ba, La Jolla, CA 92093 USA

[25] State Univ New Jersey, Inst Quantitat Biomed, Res Collab Struct Bioinformat Prot Data Ba, Rutgers, Piscataway, NJ USA

[26] TO Daniel Res Incubator & Collaborat Ctr, MBrace Therapeut, Summit, NJ USA

[27] Roche Innovat Ctr Basel, Roche Pharma Res & Early Dev, Basel, Switzerland

[28] Univ Colorado, Sch Med, Dept Pharmacol, Aurora, CO USA

[29] United Arab Emirates Univ, Off Provost, Al Ain, U Arab Emirates

来源：

ELIFE | 2021年 / 10卷

基金：

美国国家卫生研究院; 美国国家科学基金会; 英国医学研究理事会;

关键词：

IN-VIVO; STRUCTURAL BASIS; MOUSE MODEL; EXPRESSION; PEPTIDE; DISPARITIES; MECHANISM; DELIVERY; FEATURES; COMPLEX;

D O I：

10.7554/eLife.65145

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Triple-negative breast cancer (TNBC) is an aggressive tumor with limited treatment options and poor prognosis. We applied the in vivo phage display technology to isolate peptides homing to the immunosuppressive cellular microenvironment of TNBC as a strategy for nonmalignant target discovery. We identified a cyclic peptide (CSSTRESAC) that specifically binds to a vitamin D receptor, protein disulfide-isomerase A3 (PDIA3) expressed on the cell surface of tumor-associated macrophages (TAM), and targets breast cancer in syngeneic TNBC, non-TNBC xenograft, and transgenic mouse models. Systemic administration of CSSTRESAC to TNBC-bearing mice shifted the cytokine profile toward an antitumor immune response and delayed tumor growth. Moreover, CSSTRESAC enabled ligand-directed theranostic delivery to tumors and a mathematical model confirmed our experimental findings. Finally, in silico analysis showed PDIA3-expressing TAM in TNBC patients. This work uncovers a functional interplay between a cell surface vitamin D receptor in TAM and antitumor immune response that could be therapeutically exploited.

引用

页数：24

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